الفهرس 
Low birth weight & Intra Uterine Growth RestrictionOnly 14 pages are availabe for public view
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Abstract
Intrauterine growth restriction is defined as the pathologic inhibition of intrauterine fetal growth and the failure of the fetus to achieve its growth potential. Considered by the American College of Obstetricians and Gynecologists “the most common and complex problem in modern obstetrics”
One of the most common causes of IUGR is preeclampsia. Preeclampsia has remained a significant public health threat in both developed and developing countries contributing to maternal and perinatal morbidity and mortality globally.
A number of metabolic abnormalities have been observed in pregnancies complicated by intrauterine growth restriction (IUGR). Metabolic fingerprinting and clinical metabolomics have recently been proposed as tools to investigate individual phenotypes beyond genomes and proteomes and to advance hypotheses on the genesis of diseases. Non-targeted metabolomic profiling was employed to study fetal and/or placental metabolism alterations in IUGR fetuses by liquid Tandem mass spectrometry (TMS) analysis of cord blood collected soon after birth.
Samples were collected from 40 IUGR and 10 appropriate for gestational age (AGA) fetuses. Birth weight differed significantly between IUGR and AGA fetuses (p < 0.001).
The current study was a case control observational study conducted in the period from a January 2014 to December 2014 in Obstetrics and Gynecology hospital, Ain Shams University on the neonates on the first day of life. The studied groups involved 10 control full term appropriate for gestational age neonates and 40 full term IUGR neonates.
Group I: included 40 SGA neonates, 47.5 % were males and 52.5 % females. Their birth weight ranged from 800 gm - 2.4 kg, mean 1.3 kg ± 0.3 . Their crown heel length ranged from 35-45 cm, mean 40 cm ± 2.6. OFC ranged 25-32 cm, mean 28 cm ± 1.9. 25% were delivered vaginally and 75 % were delivered by C.S.
Group II was the control group. It consisted of 10 AGA neonates, 50 % were males and 50 % females. Their birth weight ranged from 2.7-3.8 kg, mean 3.2kg ± 0.4. Their crown heel length ranged from 45-51 cm, mean 48.5 cm ± 2.4. OFC ranged 33-36 , mean 34.4 cm ± 1.17 . 100 % were delivered vaginally and 0 % were delivered by C.S.
In this study we measured the metabolic profile of 40 SGA neonates; namely acylcarnitine & amino acids in comparison to 10 healthy AGA neonates with normal birth weight.
Using TMS Spectrometry, several metabolites were identified allowing a clear discrimination between IUGR and AGA samples, Amino acid patterns showed significant changes in IUGR cases supporting the existence of potential pathophysiological differences between IUGR & AGA patients.
Our results revealed that one of the major findings in our work was the altered Acylcarnitine profile.
Most acylcarnitines are derived from Fatty acid oxidation (FAO), so increased acylcarnitine indicate fatty acid oxidation defect which is a major finding in our study.
They can be formed from almost any CoA ester. Other intermediates that yield acylcarnitines are ketone bodies [C4-3OH-carnitine], degradation products of lysine, tryptophan, valine, leucine, and isoleucine (C3- and C5-carnitine and others), and carbon atoms from glucose (acetylcarnitin(.
More recently, acylcarnitine analysis is used to investigate more common metabolic derangements such as insulin resistance as long-chain acylcarnitines interfere with insulin signaling directly within the cell membrane.
As to the nature of the underlying pathophysiological mechanisms involved in these findings, abnormal acylcarnitines metabolism in IUGR could be explained by both chronic exposure to hypoxia and undernutrition.
Also in our study, glutamine levels were found to be increased in IUGRs as compared with matched controls. Glutamine concentration in fetal blood depends on the transfer from maternal blood, but also on placental synthesis.
Increased glutamine levels in severe IUGR could be explained by the inherent hypercatabolic status of IUGR. Fetal glutamine is next to glucose as one of the main sources of cellular energy in fetal life. It also plays a key role in fetal neurodevelopment being a precursor of alpha amino butyric acid, a neurotransmission inhibitor.
In the current study, we found that Phenylalanine and tyrosine levels were significantly increased.
Leucine and valine were significantly increased in IUGR. Valine and leucine, together with isoleucine, are defined as branched-chain amino acids (BCAA). Our observations suggest that changes in these amino acids could be a characteristic feature of IUGR.
Our results parameters predict diseases that can be occurred in LBW and IUGR fetuses, we divided them according to their incidence into high, intermediate and low risk groups.
Diseases which have high possibility of incidence: Ornithine Transcarbamylase deficiency (OTC), Homocystinuria due to defect of N (5,10) methylene tetrahydrofolate deficiency, methylmalonic aciduria, megaloblastic anemia due to defect in cobalamin metabolism, Histidinemia, Sotos syndrome, argininosuccinic aciduria, short bowel syndrome due to intestinal failure, 3-phosphoglycerate dehydrogenase deficiency, non ketotic hyperglycinemia, hypervalinemia, congenital glutamine deficiency, hyperinsulinism, transient tyrosinemia of the newborn, tyrosinemia type II, III, hyperornithinemia with gyrate atrophy (HOGA), triple HHH (hyperornithinemia, hyperammonemia, homocitrulllinemia), etheylmalonic encephalopathy (EPEMA), Barth syndrome, pearson syndrome, leigh like mitochondrial encephalopathy, Narp syndrome, inflammatory diseases, myocardial infarction N-acetylglutamate synthetase deficiency, citrullinemia type I, II, hyperprolinemia type I, II, hyperphenylalaninemia,
Diseases with intermediate possibility of incidence: Acute seizures, tyrosinemia I, neonatal intrahepatic cholestasis, Juvenile myoclonic epilepsy, phenylketonuria, propionic academia, glutaric aciduria, 3- hydroxyisobutyric aciduria, myopathic carnitine deficiency, Maple serup urine diseas, Hawkinsinuria.
Diseases with low possibility of incidence: Different seizures disorders, non insulin dependent diabetes miliitus, hyperargininemia, hyperthyroidism, schizophrenia, methylmalonic aciduria, pyruvate dehydrogenase deficiency (PDD), carnitine- acylcarnitine translocase deficiency, carnitine palmitoyl tranferase deficiency, isovaleric academia, long chain acyl coA dehydrogenase deficiency (LCHAD), very long chain acyl coA dehydrogenase deficiency (VLCAD), medium chain acyl coA dehydrogenase deficiency (MCAD).